Piezoelectric transducer

ABSTRACT

Devices and systems for transmitting information within a body are disclosed. An example system includes a signal generator configured for transmitting an acoustic interrogation signal, a sensor for sensing at least one parameter within the body and generating an electrical sensor signal, an acoustic transducer coupled to the sensor and configured to convert a received acoustic interrogation signal into an electrical signal, and a switching element adapted to modulate a reflected acoustic wave from the acoustic transducer based on the electrical sensor signal. The switching element is configured to controllably change the mechanical impedance of the acoustic transducer based a parameter of the electrical sensor signal, such as frequency.

CROSS REFERENCE TO RELATED APPLICATIONS

This Application is a continuation of U.S. Application Ser. No.12/578,376, filed Oct. 13, 2009, now U.S. Pat. No. 7,948,148, which is acontinuation of U.S. Application Ser. No. 10/638,405, filed Aug. 12,2003, now U.S. Pat. No. 7,621,905, which is a continuation of U.S.Application Ser. No. 09/930,455, filed Aug. 16, 2001, now abandoned, andwhich is also a continuation-in-part of U.S. Application Ser. No.10/235,968, filed Sep. 6, 2002, now U.S. Pat. No. 6,720,709, which is acontinuation of U.S. Application Ser. No. 09/691,887, filed Oct. 20,2000, now U.S. Pat. No. 6,504,286, which is a continuation of U.S.Application Ser. No. 09/000,553, filed Dec. 30, 1997, now U.S. Pat. No.6,140,740, all of which are incorporated herein by reference in theirentireties for all purposes.

FIELD AND BACKGROUND OF THE INVENTION

The present invention relates to a device for intrabody delivery ofmolecules, to a method and system of utilizing same and to a method offabricating same. More particularly, embodiments of the presentinvention relate to a drug delivery device which utilizes an acoustictransducer for generating an electrical activation signal from anacoustic signal received thereby.

The efficacy of drug treatment is oftentimes dependent upon the mode ofdrug delivery.

Localized drug delivery is oftentimes preferred since it traverseslimitations associated with systemic drug delivery including rapid druginactivation and/or ineffectual drug concentrations at the site oftreatment. In addition, in some cases, systemic drug delivery can leadto undesired cytotoxic effects at tissue regions other than that to betreated.

Since localized intrabody delivery of medication is central to efficientmedical treatment, attempts have been made to design and fabricateintrabody delivery devices which are capable of controlled and localizedrelease of a wide variety of molecules including, but not limited to,drugs and other therapeutics.

Controlled release polymeric devices have been designed to provide drugrelease over a period of time via diffusion of the drug out of thepolymer and/or degradation of the polymer over the desired time periodfollowing administration to the patient. Although these devices enablelocalized drug delivery, their relatively simple design is limited inthat it does not enable accurate and controlled delivery of the drug.

U.S. Pat. No. 5,490,962 to Cima, et al. discloses the use of threedimensional printing methods to make more complex devices which providerelease over a desired time frame, of one or more drugs. Although thegeneral procedure for making a complex device is described, specificdesigns are not detailed.

U.S. Pat. No. 4,003,379 to Ellinwood describes an implantableelectromechanically driven device that includes a flexible retractablewalled container, which receives medication from a storage area via aninlet and then dispenses the medication into the body via an outlet.

U.S. Pat. Nos. 4,146,029 and 3,692,027 to Ellinwood discloseself-powered medication systems that have programmable miniaturizeddispensing means.

U.S. Pat. No. 4,360,019 to Jassawalla discloses an implantable infusiondevice that includes an actuating means for delivery of the drug througha catheter. The actuating means includes a solenoid driven miniaturepump.

Since such devices include miniature power-driven mechanical parts whichare required to operate in the body, i.e., they must retract, dispense,or pump, they are complicated and subject to frequent breakdowns.Moreover, due to complexity and size restrictions, they are unsuitablefor delivery of more than a few drugs or drug mixtures at a time.

U.S. Pat. Nos. 6,123,861 and 5,797,898 both to Santini, Jr., et al.disclose microchip devices which control both the rate and time ofrelease of multiple chemical substances either in a continuous or apulsatile manner. Such microchip devices employ a reservoir cap which isfabricated of a material that either degrades or allows the molecules todiffuse passively out of the reservoir over time or materials thatoxidize and dissolve upon application of an electric potential. Releasefrom the microchip device can be controlled by a preprogrammedmicroprocessor, via a radiofrequency (RF) activation signal, or bybiosensors.

Although the microchip device described by Santini, Jr., et al. presentssubstantial improvements over other prior art devices, it suffers fromseveral inherent limitations which will be described in detailhereinbelow.

There is thus a widely recognized need for, and it would be highlyadvantageous to have, a delivery device and methods of fabricating andutilizing same which device can be used for accurate and timely deliveryof a drug or drugs within a body tissue region devoid of the abovelimitation.

The present invention also relates to an acoustic transducer and, inparticular, to a miniature flexural piezoelectric transducer forreceiving acoustic energy transmitted from a remote source andconverting such energy into electrical power for activating anelectronic circuit. Further, the present invention relates to aminiature flexural piezoelectric transmitter for transmitting acousticinformation by modulating the reflection of an external impingingacoustic wave.

The prior art provides various examples of piezoelectric transducers.Examples of such piezoelectric transducers are disclosed in U.S. Pat.Nos. 3,792,204; 4,793,825; 3,894,198; 3,798,473; and 4,600,855.

However, none of the prior art references provide a miniature flexuralpiezoelectric transducer specifically tailored so as to allow the usageof low frequency acoustic signals for vibrating the piezoelectric layerat its resonant frequency, wherein substantially low frequency signalsherein refer to signals having a wavelength that is much larger than thedimensions of the transducer. Further, none of the prior art referencesprovide a miniature transducer having electrodes specifically shaped soas to maximize the electrical output of the transducer. Further, none ofthe above references provide a transducer element which may beintegrally manufactured with any combination of electronic circuits byusing photolithographic and microelectronics technologies.

Further, the prior art fails to provide a miniature flexuralpiezoelectric transmitter which modulates the reflected acoustic wave bycontrollably changing the mechanical impedance of the piezoelectriclayer according to a message signal received from an electroniccomponent such as a sensor. Further, the prior art fails to provide suchtransmitter wherein the piezoelectric layer is electrically connected toa switching element, the switching element for alternately changing theelectrical connections of the transmitter so as to alternately changethe mechanical impedance of the piezoelectric layer. Further, the priorart fails to provide such transducer wherein the mechanical impedance ofthe piezoelectric layer is controlled by providing a plurality ofelectrodes attached thereto, the electrodes being electricallyinterconnected in parallel and anti-parallel electrical connections.Further, the prior art fails to provide such transmitter wherein thepiezoelectric layer features different polarities at distinct portionsthereof. Further, the prior art fails to provide such transmitter whichincludes a chamber containing a low pressure gas for enablingasymmetrical fluctuations of the piezoelectric layer. Further, the priorart fails to provide such transmitter having a two-ply piezoelectriclayer.

SUMMARY OF THE INVENTION

According to one aspect of the present invention there is provided adevice for controlled release of molecules comprising: (a) a device bodyhaving at least one reservoir therein for containing the molecules, theat least one reservoir being formed with a barrier impermeable to themolecules thereby preventing release thereof from the at least onereservoir; and (b) at least one acoustic transducer being attached to,or forming a part of, the device body, the at least one acoustictransducer being for converting an acoustic signal received thereby intoan electrical signal, the electrical signal leading to barrierpermeabilization and therefore release of the molecules from the atleast one reservoir.

According to an additional aspect of the present invention there isprovided a system for localized delivery of molecules within the bodycomprising: (a) an intrabody implantable device including: (i) a devicebody having at least one reservoir therein for containing the molecules,the at least one reservoir being formed with a barrier impermeable tothe molecules thereby preventing release thereof from the at least onereservoir; and (ii) at least one acoustic transducer being attached to,or forming a part of, the device body, the at least one acoustictransducer being for converting an acoustic signal received thereby intoan electrical signal, the electrical signal leading to barrierpermeabilization and therefore release of the molecules from the atleast one reservoir; and (b) an extracorporeal unit for generating theacoustic signal.

According to another aspect of the present invention there is provided amethod of delivering molecules to a specific body region, the methodcomprising: (a) implanting within the body region a device including:(i) a device body having at least one reservoir therein containing themolecules, the at least one reservoir being formed with a barrierimpermeable to the molecules thereby preventing release thereof from theat least one reservoir; and (ii) at least one acoustic transducer beingattached to, or forming a part of, the device body, the at least oneacoustic transducer being for converting an acoustic signal receivedthereby into an electrical signal, the electrical signal leading tobarrier permeabilization and therefore release of the molecules from theat least one reservoir; and (b) extracorporeally irradiating the bodywith an acoustic signal thereby causing the subsequent release of themolecules from the at least one reservoir.

According to further features in preferred embodiments of the inventiondescribed below, the device further comprising a cathode, and an anode,whereas the electrical signal generates an electric potential betweenthe cathode and the anode leading to permeabilization of the barrier andrelease of the molecules from the at least one reservoir.

According to still further features in the described preferredembodiments the anode is attached to or forms at least a part of thebarrier.

According to still further features in the described preferredembodiments the electrical signal directly generates the electricpotential between the cathode and the anode.

According to still further features in the described preferredembodiments the device further comprising a power source for generatingthe electric potential between the cathode and the anode upon receivingthe electrical signal from the at least one acoustic transducer.

According to still further features in the described preferredembodiments the at least one acoustic transducer serves as an acousticswitch.

According to still further features in the described preferredembodiments permeabilization of the barrier is effected by at leastpartial disintegration thereof.

According to still further features in the described preferredembodiments a type or duration of the electrical signal controls adegree of permeabilization of the barrier and thus an amount of themolecules released.

According to still further features in the described preferredembodiments the device includes a plurality of reservoirs.

According to still further features in the described preferredembodiments the device includes a plurality of acoustic transducers.

According to still further features in the described preferredembodiments each of the plurality of acoustic transducers generates anelectrical signal which leads to permeabilization of a barrier of acorresponding reservoir of the plurality of reservoirs.

According to still further features in the described preferredembodiments each of the plurality of acoustic transducers is capable ofconverting an acoustic signal of a distinct frequency or frequenciesinto the electrical signal.

According to still further features in the described preferredembodiments the plurality of reservoirs are for containing differenttypes of molecules, different amounts of molecules, or combinationsthereof.

According to still further features in the described preferredembodiments the molecules are drug molecules.

According to still further features in the described preferredembodiments the at least one acoustic transducer includes: (i) a cellmember having a cavity; (ii) a substantially flexible piezoelectriclayer attached to the cell member, the piezoelectric layer having anexternal surface and an internal surface, the piezoelectric layerfeaturing such dimensions so as to enable fluctuations thereof at itsresonance frequency upon impinging of an external acoustic wave; and(iii) a first electrode attached to the external surface and a secondelectrode attached to the internal surface.

According to still further features in the described preferredembodiments the device includes a plurality of reservoirs eachcontaining molecules of a specific type and each capable of releasingthe molecules upon provision of an acoustic signal of a specificfrequency or frequencies, such that a frequency content of the acousticsignal determines a type of the molecules released.

According to an additional aspect of the present invention there isprovided a device for controlled drug release comprising: (a) a devicebody including at least one reservoir being for containing a prodrugform of a drug, the at least one reservoir being formed with a barrierimpermeable to the prodrug thereby preventing release thereof from theat least one reservoir; and (b) at least one acoustic transducer beingattached to, or forming a part of the device body, the at least oneacoustic transducer being for converting an acoustic signal receivedthereby into an electrical signal, the electrical signal leading to aconversion of the prodrug into the drug, the drug being capable oftraversing the barrier thereby releasing from the at least onereservoir.

According to yet an additional aspect of the present invention there isprovided a system for localized delivery of molecules within the bodycomprising: (a) an intrabody implantable device including: (i) a devicebody including at least one reservoir being for containing a prodrugform of a drug, the at least one reservoir being formed with a barrierimpermeable to the prodrug thereby preventing release thereof from theat least one reservoir; and (ii) at least one acoustic transducer beingattached to, or forming a part of the device body, the at least oneacoustic transducer being for converting an acoustic signal receivedthereby into an electrical signal, the electrical signal leading to aconversion of the prodrug into the drug, the drug being capable oftraversing the barrier thereby releasing from the at least onereservoir; and (b) an extracorporeal unit for generating the acousticsignal.

According to still further features in the described preferredembodiments a type or duration of the electrical signal controls adegree of the conversion and thus an amount of the drug formed andreleased.

According to still further features in the described preferredembodiments the device includes a plurality of reservoirs and aplurality of acoustic transducers, each of the plurality of acoustictransducers generating an electrical signal which leads to theconversion of the prodrug to the drug contained in a correspondingreservoir of the plurality of reservoirs.

According to still further features in the described preferredembodiments the plurality of reservoirs are for containing differenttypes of prodrugs, different amounts of prodrugs, or combinationsthereof.

According to still an additional aspect of the present invention thereis provided a method of fabricating a device for controllable release ofmolecules, the method comprising: (a) providing a substrate; (b)configuring the substrate with the at least one reservoir; (c) cappingthe at least one reservoir with a cap material which acts as animpermeable barrier to the molecules, the material becoming permeable tothe molecules following generation of an electrical potential in oraround the at least one reservoir; and (d) providing an inlet port forfilling the at least one reservoir with the molecules, the inlet beingsealable following the filling, thereby generating the device forcontrollable release of molecules.

According to still further features in the described preferredembodiments the method further comprising the step of: (e) attaching to,or fabricating within, the substrate, at least one acoustic transducer,the at least one acoustic transducer being for generating an electricalsignal from an acoustic signal received thereby, the electrical signalleading to generation of the electrical potential in or around the atleast one reservoir.

According to still further features in the described preferredembodiments the at least one acoustic transducer includes: (i) a cellmember having a cavity; (ii) a substantially flexible piezoelectriclayer attached to the cell member, the piezoelectric layer having anexternal surface and an internal surface, the piezoelectric layerfeaturing such dimensions so as to enable fluctuations thereof at itsresonance frequency upon impinging of an external acoustic wave; and(iii) a first electrode attached to the external surface and a secondelectrode attached to the internal surface.

According to still further features in the described preferredembodiments step (b) is effected by etching the substrate.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a device, system and methodfor efficient intrabody delivery of molecules such as drugs as well as amethod of manufacture.

The present invention also relates to a miniature flexural transducerelement, comprising, (a) a cell element having a cavity; (b) asubstantially flexible piezoelectric layer attached to the cell member,the piezoelectric layer having an external surface and an internalsurface, the piezoelectric layer featuring such dimensions so as toenable fluctuations thereof at its resonance frequency upon impinging ofan external acoustic wave; and (c) a first electrode attached to theexternal surface and a second electrode attached to the internal surfaceof the piezoelectric layer. Preferably, the cavity is etched into asubstrate including an electrically insulating layer and an electricallyconducting layer. The first electrode is preferably integrally made witha substantially thin electrically conducting layer, the electricallyconducting layer being disposed on the substrate and connected theretoby a sealing connection. The cell member may be circular or hexagonal incross section. According to further features in preferred embodiments ofthe invention described below, the substrate may include a plurality ofcell members electrically connected in parallel or serial connections.Preferably, at least one of the electrodes is specifically shaped so asto provide a maximal electrical output, wherein the electrical outputmay be current, voltage or power. A preferred shape of the electrodesincludes two cores interconnected by a connecting member. A transducerelement according to the present invention may also be used as atransmitter.

Preferably, the cavity of the transducer element includes gas of lowpressure so as to allow its usage as a transmitter. According to thepresent invention there is further provided a transmitter element,comprising: (a) a cell element having a cavity; (b) a substantiallyflexible piezoelectric layer attached to the cell member, thepiezoelectric layer having an external surface and an internal surface,the piezoelectric layer featuring such dimensions so as to enablefluctuations thereof at its resonance frequency upon impinging of anexternal acoustic wave; and (c) a first electrode attached to theexternal surface and a second electrode attached to the internal surfaceof the piezoelectric layer, the electrodes being electrically connectedto an electrical circuit including a switching element for controllablychanging the mechanical impedance of the piezoelectric layer.Preferably, the switching frequency of the switching element equals thefrequency of an electrical message signal arriving from an electronicmember, such as a sensor, thereby modulating a reflected acoustic waveaccording to the frequency of the message signal. The transmitterelement may include a third electrode attached to the external surfaceand a fourth electrode attached to the internal surface of thepiezoelectric layer. When using such a configuration, the switchingelement preferably alternately connects the electrodes in parallel andanti-parallel, thereby controllably changing the mechanical impedance ofthe piezoelectric layer. According to a specific configuration, theelectrodes are interconnected by means of a built-in anti-parallelelectrical connection. Alternatively, the electrodes may beinterconnected by means of a built-in parallel electrical connection.The switching element may be an on/off switch. According to anotherembodiment, the piezoelectric layer includes first and second portionshaving opposite polarities. According to yet another embodiment, thetransmitter element may include two cell members electricallyinterconnected by means of a built-in parallel or anti-parallelelectrical connection. Alternatively, the switching element mayalternately connect the cell members in parallel and anti-parallelelectrical connections. The cell members may have piezoelectric layersof opposite polarities. According to yet another embodiment the cavityof the transmitter element is covered by a two-ply piezoelectric layerincluding an upper layer bonded to a lower layer. The upper and lowerlayers may feature opposite polarities. The upper and lower layers maybe separated by an insulating layer disposed therebetween.

Further according to the present invention there is provided a method oftransmitting acoustic information, comprising: (a) providing asubstantially flexible piezoelectric layer having first and secondelectrodes attached thereto, the piezoelectric layer being attached to acell member, the electrodes being electrically connected to anelectrical circuit including a switching element; (b) providing anacoustic wave for impinging on the piezoelectric layer, the acousticwave having a reflected portion; (c) modulating the reflected portion ofthe acoustic wave by controlling the mechanical impedance of thepiezoelectric layer, said controlling by switching the switching elementat a frequency which equals the frequency of a message signal arrivingfrom an electronic component such as a sensor. The method may furthercomprise: (a) providing third and fourth electrodes attached to thepiezoelectric layer, the third and fourth electrodes being electricallyconnected to the electrical circuit; (b) changing the electricalconnections between the electrodes by means of the switching element soas to change the mechanical impedance of the piezoelectric layer.According to a specific configuration, the first and second electrodesare attached to a first cell member and the third and fourth electrodesare attached to a second cell member.

The present invention successfully addresses the shortcomings of thepresently known configurations by providing a miniature flexuralpiezoelectric transducer specifically tailored so as to allow the usageof low frequency acoustic signals for vibrating the piezoelectric layerat its resonant frequency, wherein substantially low frequency signalsherein refer to signals having a wavelength that is much larger thandimensions of the transducer. Further, the present invention addressesthe shortcomings of the presently known configurations by providing suchtransducer element having electrodes specifically shaped so as tomaximize the electrical output of the transducer, and which may beintegrally manufactured with any combination of electronic circuits byusing photolithographic and microelectronics technologies.

Further, the present invention addresses the shortcomings of thepresently known configurations by providing a miniature flexuralpiezoelectric transmitter which modulates a reflected acoustic wave bycontrollably changing the mechanical impedance of the piezoelectriclayer according to a message signal received from an electroniccomponent such as a sensor. Further, the present invention addresses theshortcomings of the presently known configurations by providing suchtransmitter wherein the mechanical impedance of the piezoelectric layeris controlled by providing a plurality of electrodes attached thereto,the electrodes being interconnected in parallel and anti-parallelelectrical connections, and wherein at least a portion of the electrodesis electrically connected to a switching element, the switching elementfor alternately changing the electrical connections between theelectrodes so as to alternately change the mechanical impedance of thepiezoelectric layer.

BRIEF DESCRIPTION OF THE DRAWINGS

The invention is herein described, by way of example only, withreference to the accompanying drawings. With specific reference now tothe drawings in detail, it is stressed that the particulars shown are byway of example and for purposes of illustrative discussion of thepreferred embodiments of the present invention only, and are presentedin the cause of providing what is believed to be the most useful andreadily understood description of the principles and conceptual aspectsof the invention. In this regard, no attempt is made to show structuraldetails of the invention in more detail than is necessary for afundamental understanding of the invention, the description taken withthe drawings making apparent to those skilled in the art how the severalforms of the invention may be embodied in practice.

FIG. 1 is a cross sectional view of a general configuration of thedevice of the present invention;

FIG. 2 a is a longitudinal section of a transducer element according tothe present invention taken along lines A-A in FIGS. 3 a-3 e;

FIG. 2 b is a longitudinal section of a transducer element according tothe present invention taken along lines B-B in FIGS. 3 a-3 e;

FIG. 3 a is a cross section of a transducer element according to thepresent invention taken along line C-C in FIG. 2 a;

FIG. 3 b is a cross section of a transducer element according to thepresent invention taken along line D-D in FIG. 2 a;

FIG. 3 c is a cross section of a transducer element according to thepresent invention taken along line E-E in FIG. 2 a;

FIG. 3 d is a cross section of a transducer element according to thepresent invention taken along line F-F in FIG. 2 a;

FIG. 3 e is a cross section of a transducer element according to thepresent invention taken along line G-G in FIG. 2 a;

FIG. 4 shows the distribution of charge density across a piezoelectriclayer of a transducer element resulting from the application of aconstant pressure over the entire surface of the layer;

FIGS. 5 a-5 d show the results of optimization performed for the powerresponse of a transducer according to the present invention;

FIG. 6 shows a preferred electrode shape for maximizing the powerresponse of a transducer according to the present invention;

FIG. 7 is a longitudinal section of another embodiment of a transducerelement according to the present invention capable of functioning as atransmitter;

FIG. 8 a-8 f are schematic views of possible configurations oftransmitters according to the present invention including parallel andanti-parallel electrical connections for controllably changing themechanical impedance of the piezoelectric layer;

FIG. 9 is a longitudinal section of a transmitter element according tothe present invention including an anti-parallel electrical connection;

FIG. 10 is a longitudinal section of another embodiment of a transmitterelement according to the present invention;

FIG. 11 illustrates a direct activation configuration of a moleculedelivery device of the present invention;

FIG. 12 illustrates an indirect activation configuration of a moleculedelivery device of the present invention;

FIG. 13 is a schematic diagram illustrating an acoustic switchutilizable by a device of the present invention;

FIG. 14 is a black box diagram of a drug delivery system according tothe teachings of the present invention; and

FIG. 15 is schematic diagram illustrating a control circuitry of theacoustic switch illustrated in FIG. 13.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

The present invention is of a device, system, and method which can beused for localized intrabody delivery of molecules. Specifically, thepresent invention can be used to release molecules such as drugs withina specific body region using an acoustic activation signal provided fromoutside the body.

The principles and operation of the present invention may be betterunderstood with reference to the drawings and accompanying descriptions.

Before explaining at least one embodiment of the invention in detail, itis to be understood that the invention is not limited in its applicationto the details of construction and the arrangement of the components setforth in the following description or illustrated in the drawings. Theinvention is capable of other embodiments or of being practiced orcarried out in various ways. Also, it is to be understood that thephraseology and terminology employed herein is for the purpose ofdescription and should not be regarded as limiting.

Referring now to the drawings, FIG. 1 illustrates a device forcontrolled release of molecules, which is referred to herein as device10.

Device 10 includes a device body 12 having at least one reservoir 14formed therein for containing the molecules to be delivered.

Preferably, device body 12 includes a plurality of reservoirs 14 (fourshown in FIG. 1) each being configured for containing therapeuticmolecules such as drugs and/or diagnostic molecules such as dyespreferably in a solution or as a suspension. Reservoirs 14 can be ofvarious dimensions depending on the molecule type and quantity to bedelivered therefrom.

Device body 12 can be of a planar shape; spheroidal shape or any shapesuitable for intrabody implantation and delivery of molecules storedthereby. Reservoirs 14 can be formed within a surface of device body 12or within an interior volume thereof, provided molecules releasedtherefrom can disperse into a medium surrounding device 10.

The dimensions of device 10 are limited by the site of implantation anddelivery, the quantity of drugs or drugs to be delivered thereby, andthe specific components used thereby for drug release activation.

Reservoirs 14 can be formed within device body 12 using any method knownin the art including, but not limited to, etching, machining and thelike. Alternatively, device body 12 may be pre-formed with reservoirs 14by, for example, casting or milling techniques.

Device body 12 is fabricated from a material which is impermeable to themolecules to be delivered and to the surrounding fluids, for example,water, blood, electrolytes or other solutions. Examples of suitablematerials include ceramics, semiconductors, biological membranes, anddegradable and non-degradable polymers; biocompatibility is preferred,but not required.

For in-vivo applications, non-biocompatible materials may beencapsulated in a biocompatible material, such as polyethyleneglycol orpolytetrafluoroethylene-like materials, before use. One example of astrong, non-degradable, easily etched substrate that is impermeable tothe molecules to be delivered and the surrounding fluids is silicon.

Alternatively, device body 12 can also be fabricated from a materialwhich degrades or dissolves over a period of time into biocompatiblecomponents such as Polyvinyl Alcohol (PVA). This embodiment is preferredfor in vivo applications where the device is implanted and physicalremoval of the device at a later time is not feasible or recommended, asis the case with, for example, brain implants. An example of a class ofstrong, biocompatible materials are the poly(anhydride-co-imides)discussed by K. E. Uhrich et al., “Synthesis and characterization ofdegradable poly(anhydride-co-imides)”, Macromolecules, 1995, 28,2184-93.

Reservoir 14 is formed (capped) with a barrier 16 which is impermeableto the molecules to be delivered. As such barrier 16 serves forpreventing molecules contained within reservoir 14 from releasing intothe surrounding medium when device 10 is implanted within the body.

Reservoir 14 can be filled with molecules of interest either prior tocapping with barrier 16 or following such capping. In the latter case,reservoir 14 also includes an inlet port 18, which serves for fillingreservoir 14 with molecules of choice following fabrication of device10. Inlet port 18 is designed to be sealable following filling, suchthat accidental drug release therefrom does not occur.

Device 10 further includes at least one acoustic transducer 20. Acoustictransducer 20 can be attached to, or it can form a part of, device body12. Acoustic transducer 20 serves for converting an acoustic signalreceived thereby into an electrical signal. The electrical signalgenerated by transducer 20 is preferably rectified via a full orhalf-bridge rectifier into a DC current signal. The converted electricalsignal can be used to directly or indirectly release the moleculesstored in reservoir 14 as described hereinbelow.

According to a preferred embodiment of the present invention, theelectrical signal generates (directly or indirectly) an electricalpotential within reservoir 14.

To this end, device 10 further includes at least one pair of electrodes21, which are preferably positioned within reservoir 14 and which servefor providing the electrical potential therein.

According to one preferred embodiment of the present invention, theelectrical potential converts the molecules stored within reservoir 14into an active and barrier permeable form.

For example, the molecules contained within reservoir 14 can be providedas large aggregates which are unable to traverse barrier 16 which canbe, in this case, a size selective membrane. Upon provision of theelectrical potential the molecules disaggregate into smaller activeunits which are able to diffuse out of reservoir 14 through barrier 16.

According to another preferred embodiment of the present invention, theelectrical potential leads to permeabilization of barrier 16 andsubsequent release of the molecules from reservoir 14.

For example, the electrical potential generated by electrodes 21 cancause the partial or full disintegration of barrier 16 and as such therelease of the molecules from reservoir 14.

In such a case, barrier 16 can be composed of a thin film of conductivematerial that is deposited over the reservoir, patterned to a desiredgeometry, and functions as an anode 22. The size and placement ofcathode 23 depends upon the device's application and method of electricpotential control.

Conductive materials capable of dissolving into solution or formingsoluble compounds or ions upon the application of an electric potential,include, but are not limited to, metals such as copper, gold, silver,and zinc and some polymers.

Thus, according to this configuration of device 10, when an electricpotential is applied between anode 22 and cathode 23, the conductivematerial of the anode above the reservoir oxidizes to form solublecompounds or ions that dissolve into solution, exposing the molecules tobe delivered to the surrounding medium.

Alternatively, the application of an electric potential can be used tocreate changes in local pH near barrier 16 thereby leading to dissolvingof barrier 16 and release of the molecules.

Still alternatively, the application of an electric potential can beused to create changes in the net charge of barrier 16 or the net chargeor solubility of the molecules thereby enabling barrier 16 traversing.

In any case, the molecules to be delivered are released into thesurrounding medium by diffusion out of or by degradation or dissolutionof the release system. The frequency and quantity of release can becontrolled via the acoustic signal received by acoustic transducer 20 asis further described hereinbelow.

FIGS. 2 a, 2 b and 3 a-3 e illustrate a preferred embodiment of atransducer element according to the present invention. As shown in thefigures, the transducer element 20 includes at least one cell member 25including a cavity 24 etched or drilled into a substrate and covered bya substantially flexible piezoelectric layer 26. Attached topiezoelectric layer 26 are an upper electrode 28 and a lower electrode30 which are connectable to an electronic circuit. The substrate ispreferably made of an electrical conducting layer 32 disposed on anelectrically insulating layer 34, such that cavity 24 is etchedsubstantially through the thickness of electrically conducting layer 32.

Electrically conducting layer 32 is preferably made of copper andinsulating layer 34 is preferably made of a polymer such as polyimide.Conventional copper-plated polymer laminate such as KAPTON sheets may beused for the production of transducer 20. Commercially availablelaminates such as NOVOCLAD may be used. Alternatively, the substrate mayinclude a silicon layer, or any other suitable material. Alternatively,layer 32 is made of a non-conductive material such as PYRALIN.

Preferably, cavity 24 is etched into the substrate by using conventionalprinted-circuit photolithography methods. Alternatively, cavity 24 maybe etched into the substrate by using VLSI/micro-machining technology orany other suitable technology.

Piezoelectric layer 26 may be made of PVDF or a copolymer thereof.Alternatively, piezoelectric layer 26 is made of a substantiallyflexible piezoceramic. Preferably, piezoelectric layer 26 is a poledPVDF sheet having a thickness of about 9-28 μm.

Preferably, the thickness and radius of flexible layer 26, as well asthe pressure within cavity 24, are specifically selected so as toprovide a predetermined resonant frequency. When using the embodiment ofFIGS. 2 a and 2 b, the radius of layer 26 is defined by the radius ofcavity 24.

By using a substantially flexible piezoelectric layer 26, the presentinvention allows to provide a miniature transducer element whoseresonant frequency is such that the acoustic wavelength is much largerthan the extent of the transducer. This enables the transducer to beomnidirectional even at resonance, and further allows the use ofrelatively low frequency acoustic signals which do not suffer fromsignificant attenuation in the surrounding medium.

Prior art designs of miniature transducers, however, rely on rigidpiezoceramic usually operating in thickness mode. In such cases theresonant frequency relates to the size of the element and speed of soundin the piezoceramic, and is higher by several orders of magnitude.

The present invention provides a transducer which is omnidirectional,i.e., insensitive to the direction of the impinging acoustic rays,thereby substantially simplifying the transducer's operation relative toother resonant devices. Such a transducer element is thus suitable forapplication in confined or hidden locations, where the orientation ofthe transducer element cannot be ascertained in advance.

The configuration and acoustic properties of such an acoustic transducerand variants thereof as well as general acoustic transduction principlesare described in detail in U.S. Pat. No. 6,140,740 and PCT PublicationNo. WO 99/34,453 the disclosures of which are expressly incorporated byreference as if fully set forth herein.

According to a specific embodiment, cavity 24 features a circular orhexagonal shape with radius of about 200 μm. Electrically conductinglayer 32 preferably has a thickness of about 15 μm. Cell member 25 ispreferably etched completely through the thickness of electricallyconducting layer 32.

Electrically insulating layer 34 preferably features a thickness ofabout 50 μm. The precise dimensions of the various elements of atransducer element according to the present invention may bespecifically tailored according to the requirements of the specificapplication.

Cavity 24 preferably includes a gas such as air. The pressure of gaswithin cavity 24 may be specifically selected so as to predetermine thesensitivity and ruggedness of the transducer as well as the resonantfrequency of layer 26.

As shown in FIG. 3 b, an insulating chamber 36 is etched into thesubstrate, preferably through the thickness of conducting layer 32, soas to insulate the transducer element from other portions of thesubstrate which may include other electrical components such as othertransducer elements etched into the substrate. According to a specificembodiment, the width of insulating chamber 36 is about 100 μm. Asshown, insulating chamber 36 is etched into the substrate so as to forma wall 38 of a predetermined thickness enclosing cavity 24, and aconducting line 40 integrally made with wall 38 for connecting thetransducer element to another electronic component preferably etchedinto the same substrate, or to an external electronic circuit.

As shown in FIGS. 2 a and 2 b, attached to piezoelectric layer 26 areupper electrode 28 and lower electrode 30. As shown in FIGS. 3 c and 3e, upper electrode 28 and lower electrode 30 are preferably preciselyshaped so as to cover a predetermined area of piezoelectric layer 26.Electrodes 28 and 30 may be deposited on the upper and lower surfaces ofpiezoelectric membrane 26, respectively, by using various methods suchas vacuum deposition, mask etching, painting, and the like.

As shown in FIG. 2 a, lower electrode 30 is preferably made as anintegral part of a substantially thin electrically conducting layer 42disposed on electrically conducting layer 32. Preferably, electricallyconducting layer 42 is made of a Nickel-Copper alloy and is attached toelectrically conducting layer 32 by means of a sealing connection 44.Sealing connection 44 may be made of indium. According to a preferredconfiguration, sealing connection 44 may feature a thickness of about 10μm, such that the overall height of wall 38 of cavity 24 is about 20-25μm.

As shown in FIG. 3 c, electrically conducting layer 42 covers thevarious portions of conducting layer 32, including wall 38 andconducting line 40. The portion of conducting layer 42 coveringconducting line 40 is for connection to an electronic component such asa neighboring cell.

According to a preferred embodiment of the present invention, electrodes28 and 30 are specifically shaped to include the most energy-productiveregion of piezoelectric layer 26 so as to provide maximal response ofthe transducer while optimizing the electrode area, and therefore thecell capacitance, thereby maximizing a selected parameter such asvoltage sensitivity, current sensitivity, or power sensitivity of thetransducer element.

The vertical displacement of piezoelectric layer 26, ψ, resulting from amonochromatic excitation at angular frequency ω is modeled using thestandard equation for thin plates:

${{\left( {\nabla^{2}{- \gamma^{2}}} \right)\left( {\nabla^{2}{+ \gamma^{2}}} \right)\Psi} - {\frac{3\left( {1 - v^{2}} \right)}{2{Qh}^{3}}P} + {\frac{3{\mathbb{i}}\; Z\;{\omega\left( {1 - v^{2}} \right)}}{2{Qh}^{3}}\Psi}} = 0$wherein Q is the Young's modulus representing the elasticity of layer26; h the half-thickness of layer 26; v is the Poisson ratio for layer26; γ is the effective wavenumber in the layer given by:γ⁴=3ρ(1−v²)ω²/Oh², wherein ρ is the density of layer 26 and ω is theangular frequency of the applied pressure (wherein the applied pressuremay include the acoustic pressure, the static pressure differentialacross layer 26 and any other pressure the transducer comes across); Zis the mechanical impedance resulting from the coupling of layer 26 toboth external and internal media of cavity 24, wherein the internalmedium is preferably air and the external medium is preferably fluid; Pis the acoustic pressure applied to layer 26, and Ψ represents theaverage vertical displacement of layer 26.

When chamber 24 is circular, the solution (given for a single frequencycomponent ω) representing the dynamic displacement of a circular layer26 having a predetermined radius a, expressed in polar coordinates, is:

${\Psi\left( {r,\varphi} \right)} = {\frac{{{I_{1}\left( {\gamma\; a} \right)}\left\lbrack {{J_{0}\left( {\gamma\; r} \right)} - {J_{0}\left( {\gamma\; a} \right)}} \right\rbrack} + {{J_{1}\left( {\gamma\; a} \right)}\left\lbrack {{I_{0}\left( {\gamma\; r} \right)} - {I_{0}\left( {\gamma\; a} \right)}} \right\rbrack}}{{2h\;{\rho\omega}^{2}{L_{0}\left( {\gamma\; a} \right)}} + {{\mathbb{i}\omega}\;{{ZL}_{2}\left( {\gamma\; a} \right)}}}P}$L₀(z) = I₀(z)J₁(z) + J₀(z)I₁(z), L₂(z) = J₂(z)I₁(z) − I₂(z)J₁(z)$Z = {\frac{P_{A}}{{\mathbb{i}\omega}\; H_{A}} + {{{\mathbb{i}}\left\lbrack {\frac{4}{3\pi} + \frac{1}{6}} \right\rbrack}{\varphi\rho}_{W}a}}$wherein:

ψ(r,φ) is time-dependent and represents the displacement of a selectedpoint located on circular layer 26, the specific location of which isgiven by radius r and angle ω);

J and I are the normal and modified Bessel functions of the first kind,respectively;

P_(A), H_(A) are the air pressure within cavity 24 and the height ofchamber 24, respectively; and

ρ_(W) is the density of the fluid external to cavity 24.

The first term of the impedance Z relates to the stiffness resultingfrom compression of air within cavity 24, and the second term of Zrelates to the mass added by the fluid boundary layer. An additionalterm of the impedance Z relating to the radiated acoustic energy issubstantially negligible in this example.

The charge collected between electrodes 28 and 30 per unit area isobtained by evaluating the strains in layer 26 resulting from thedisplacements, and multiplying by the pertinent off-diagonal elements ofthe piezoelectric strain coefficient tensor, e₃₁, e₃₂, as follows:

${Q\left( {r,\varphi,t} \right)} = {\left( {e_{31}\left( \frac{\partial\Psi}{\partial x} \right)} \right)^{2} + \left( {e_{32}\left( \frac{\partial\Psi}{\partial y} \right)} \right)^{2}}$wherein:

Q(r,φ,t) represents the charge density at a selected point located oncircular layer 26, the specific location of which is given by radius rand angle φ;

x is the stretch direction of piezoelectric layer 26;

y is the transverse direction (the direction perpendicular to thestretch direction) of layer 26;

e₃₁, e₃₂ are off-diagonal elements of the piezoelectric straincoefficient tensor representing the charge accumulated at a selectedpoint on layer 26 due to a given strain along the x and y directions,respectively, which coefficients being substantially dissimilar whenusing a PVDF layer; and

ψ is the displacement of layer 26, taken as the sum of the displacementfor a given acoustic pressure P at frequency f, and the staticdisplacement resulting from the pressure differential between theinterior and exterior of cavity 24, which displacements beingextractable from the equations given above.

The total charge accumulated between electrodes 28 and 30 is obtained byintegrating Q(r,φ,t) over the entire area S of the electrode:Q=∫ _(S) Q(r,φ,t)d xThe capacitance C of piezoelectric layer 26 is given by:

${C = {\frac{ɛ}{2h}{\int_{S}{\mathbb{d}\overset{\_}{x}}}}},$wherein ∈ is the dielectric constant of piezoelectric layer 26; and 2 his the thickness of piezoelectric layer 26.

Accordingly, the voltage, current and power responses of piezoelectriclayer 26 are evaluated as follows:

${V = \frac{2h{\int_{N}{{Q\left( {r,\varphi,t} \right)}{\mathbb{d}\overset{\_}{x}}}}}{ɛ{\int_{N}{\mathbb{d}\overset{\_}{x}}}}},{I = {2{\mathbb{i}\omega}{\int_{S}{{Q\left( {r,\varphi,t} \right)}{\mathbb{d}\overset{\_}{x}}}}}},{W = \frac{4{\mathbb{i}}\;{h\left\lbrack {\int_{S}{{Q\left( {r,\varphi,t} \right)}{\mathbb{d}\overset{\_}{x}}}} \right\rbrack}^{2}}{ɛ{\int_{S}{\mathbb{d}\overset{\_}{x}}}}}$

The DC components of Q are usually removed prior to the evaluation,since the DC currents are usually filtered out. The values of Q givenabove represent peak values of the AC components of Q, and should bemodified accordingly so as to obtain other required values such as RMSvalues.

According to the above, the electrical output of the transducerexpressed in terms of voltage, current and power responses depend on theAC components of Q, and on the shape S of the electrodes. Further, ascan be seen from the above equations, the voltage response of thetransducer may be substantially maximized by minimizing the area of theelectrode. The current response, however, may be substantially maximizedby maximizing the area of the electrode.

FIG. 4 shows the distribution of charge density on a circularpiezoelectric layer 26 obtained as a result of pressure (acoustic andhydrostatic) applied uniformly over the entire area of layer 26, whereinspecific locations on layer 26 are herein defined by using Cartesiancoordinates including the stretch direction (x direction) and thetransverse direction (y direction) of layer 26. It can be seen thatdistinct locations on layer 26 contribute differently to the chargedensity. The charge density vanishes at the external periphery 70 and atthe center 72 of layer 26 due to minimal deformation of these portions.The charge density is maximal at two cores 74 a and 74 b locatedsymmetrically on each side of center 72 due to maximal strains (in thestretch direction) of these portions.

A preferred strategy for optimizing the electric responses of thetransducer is to shape the electrode by selecting the areas contributingat least a selected threshold percentage of the maximal charge density,wherein the threshold value is the parameter to be optimized. Athreshold value of 0% relates to an electrode covering the entire areaof layer 26.

FIGS. 5 a-5 d show the results of an optimization performed for thepower response of a transducer having a layer 26 of a predeterminedarea. As shown in the figures, the threshold value which provides anoptimal power response is about 30% (FIG. 5 b). Accordingly, anelectrode which covers only the portions of layer 26 contributing atleast 30% of the maximal charge density yields a maximal power response.The pertinent voltage response obtained by such an electrode is higherby a factor of 2 relative to an electrode completely covering layer 26(FIG. 5 a). The current response obtained by such electrode is slightlylower relative to an electrode completely covering layer 26 (FIG. 5 c).Further as shown in the figures, the deflection of layer 26 is maximalwhen applying an acoustic signal at the resonant frequency of layer 26(FIG. 5 d).

A preferred electrode shape for maximizing the power response of thetransducer is shown in FIG. 6, wherein the electrode includes twoelectrode portions 80 a and 80 b substantially covering the maximalcharge density portions of layer 26, the electrode portions beinginterconnected by means of a connecting member 82 having a minimal area.Preferably, portions 80 a and 80 b cover the portions of layer 26 whichyield at least a selected threshold (e.g. 30%) of the maximal chargedensity.

According to the present invention any other parameter may be optimizedso as to determine the shape of electrodes 28 and 30. According tofurther features of the present invention, only one electrode (upperelectrode 28 or lower electrode 30) may be shaped so as to providemaximal electrical response of the transducer, with the other electrodecovering the entire area of layer 26. Since the charge is collected onlyat the portions of layer 26 received between upper electrode 28 andlower electrode 30, such configuration is operatively equivalent to aconfiguration including two shaped electrodes having identical shapes.

Referring now to FIG. 7, according to another embodiment of the presentinvention chamber 24 of transducer element 20 may contain gas ofsubstantially low pressure, thereby conferring a substantially concaveshape to piezoelectric membrane 26 at equilibrium. Such configurationenables to further increase the electrical response of the transducer byincreasing the total charge obtained for a given displacement of layer26. The total displacement in such an embodiment is given by:ψ=ρ₀ψ_(DC)+ρψ_(AC) cos ωt, wherein P₀ is the static pressuredifferential between the exterior and the interior of cavity 24; ψ_(DC)is the displacement resulting from P₀; P is the amplitude of theacoustic pressure; and ψ_(DC) the displacement resulting from P.

Accordingly, the strain along the x direction includes three terms asfollows:

$\begin{matrix}{S_{xx} = \left( \frac{\partial\Psi}{\partial x} \right)^{2}} \\{= {\left( {P_{0}^{2}\left( \frac{\partial\Psi_{DC}}{\partial x} \right)} \right)^{2} + {\left( {P^{2}\left( \frac{\partial\Psi_{AC}}{\partial x} \right)} \right)^{2}\cos^{2}\omega\; t} +}} \\{2P_{0}P\frac{\partial\Psi_{DC}}{\partial x}\frac{\partial\Psi_{AC}}{\partial x}\cos\;\omega\; t}\end{matrix}$wherein the DC component is usually filtered out.

Thus, by decreasing the pressure of the medium (preferably air) withincavity 24 relative to the pressure of the external medium (preferablyfluid), the value of P₀ is increased, thereby increasing the value ofthe third term of the above equation.

Such embodiment of the present invention makes it possible to increasethe charge output of layer 26 for a given displacement, therebyincreasing the voltage, current and power responses of the transducerwithout having to increase the acoustic pressure P. Further, suchembodiment enables to further miniaturize the transducer since the sameelectrical response may obtain for smaller acoustic deflections. Suchembodiment is substantially more robust mechanically and therefore moredurable than the embodiment shown in FIGS. 2 a and 2 b. Such furtherminiaturization of the transducer enables to use higher resonancefrequencies relative to the embodiment shown in FIGS. 2 a and 2 b.

Preferably, a transducer element 20 according to the present inventionis fabricated by using technologies which are in wide use in themicroelectronics industry so as to allow integration thereof with otherconventional electronic components. When the transducer element includesa substrate such as Copper-polymer laminate or silicon, a variety ofconventional electronic components may be fabricated onto the samesubstrate.

According to the present invention, a plurality of cavities 24 may beetched into a single substrate 34 and covered by a single piezoelectriclayer 26 so as to provide a transducer element including a matrix oftransducing cells members 25, thereby providing a larger energycollecting area of predetermined dimensions while still retaining theadvantage of miniature individual transducing cell members 25. Whenusing such configuration, the transducing cell members 25 may beelectrically interconnected in parallel or serial connections, orcombinations thereof, so as to tailor the voltage and current responseof the transducer. Parallel connections are preferably used so as toincrease the current output while serial connections are preferably usedso as to increase the voltage output of the transducer.

Further, piezoelectric layer 26 may be completely depolarized and thenrepolarized at specific regions thereof so as to provide a predeterminedpolarity to each of the transducing cell members 25. Such configurationreduces the complexity of interconnections between the cell members 25.

A transducer element according to the present invention may be furtherused as a transmitter for transmitting information to a remote receiverby modulating the reflection of an external impinging acoustic wavearrived from a remote transmitter

Referring to FIG. 7, the transducer element shown may function as atransmitter element due to the asymmetric fluctuations of piezoelectriclayer 26 with respect to positive and negative transient acousticpressures obtained as a result of the pressure differential between theinterior and exterior of cavity 24.

A transmitter element according to the present invention preferablymodulates the reflection of an external impinging acoustic wave by meansof a switching element connected thereto. The switching element encodesthe information that is to be transmitted, such as the output of asensor, thereby frequency modulating a reflected acoustic wave.

Such configuration requires very little expenditure of energy from thetransmitting module itself, since the acoustic wave that is received isexternally generated, such that the only energy required fortransmission is the energy of modulation.

Specifically, the reflected acoustic signal is modulated by switchingthe switching element according to the frequency of a message electricsignal arriving from another electronic component such as a sensor, soas to controllably change the mechanical impedance of layer 26 accordingto the frequency of the message signal.

Preferably, the invention uses a specific array of electrodes connectedto a single cell member 25 or alternatively to a plurality of cellmembers 25 so as to control the mechanical impedance of layer 26.

FIGS. 8 a-8 g illustrate possible configurations for controllablychanging the impedance of layer 26 of a transmitter element. Referringto FIG. 8 a, a transmitter element according to the present inventionmay include a first and second pairs of electrodes, the first pairincluding an upper electrode 40 a and a lower electrode 38 a, and thesecond pair including an upper electrode 40 b and a lower electrode 38b. Electrodes 38 a, 38 b, 40 a and 40 b are electrically connected to anelectrical circuit by means of conducting lines 36 a, 36 b, 34 a and 34b, respectively, the electrical circuit including a switching element(not shown) so as to alternately change the electrical connections ofconducting lines 36 a, 36 b, 34 a and 34 b.

Preferably, the switching element switches between a parallel connectionand an anti-parallel connection of the electrodes. A parallel connectiondecreases the mechanical impedance of layer 26, wherein an anti-parallelconnection increases the mechanical impedance of layer 26. Ananti-parallel connection may be obtained by interconnecting line 34 a to36 b and line 34 b to 36 a. A parallel connection may be obtained byconnecting line 34 a to 34 b and line 36 a to 36 b. Preferably, theswitching frequency equals the frequency of a message signal arrivingfrom an electrical component such as a sensor.

According to another embodiment (FIG. 8 b), upper electrode 40 a isconnected to lower electrode 38 b by means of a conducting line 60, andelectrodes 38 a and 40 b are connected to an electrical circuit by meansof conducting lines 62 and 64, respectively, the electrical circuitincluding a switching element. Such configuration provides ananti-parallel connection of the electrodes, wherein the switchingelement functions as an on/off switch, thereby alternately increasingthe mechanical impedance of layer 26.

In order to reduce the complexity of the electrical connections, layer26 may be depolarized and then repolarized at specific regions thereof.As shown in FIG. 8 c, the polarity of the portion of layer 26 receivedbetween electrodes 40 a and 38 a is opposite to the polarity of theportion of layer 26 received between electrodes 40 b and 38 b. Ananti-parallel connection is thus achieved by interconnecting electrodes38 a and 38 b by means of a conducting line 60, and providing conductinglines 62 and 64 connected to electrodes 40 a and 40 b, respectively, theconducting lines for connection to an electrical circuit including aswitching element.

According to another embodiment, the transmitting element includes aplurality of transducing cell members, such that the mechanicalimpedance of layer 26 is controllably changed by appropriatelyinterconnecting the cell members.

As shown in FIG. 8 d, a first transducing cell member 25 a including alayer 26 a and a cavity 24 a, and a second transducing cell member 25 bincluding a layer 26 b and a cavity 24 b are preferably contained withinthe same substrate; and layers 26 a and 26 b are preferably integrallymade (not shown). A first pair of electrodes including electrodes 28 aand 30 a is attached to layer 26, and a second pair of electrodesincluding electrodes 28 b and 30 b is attached to layer 26 b. Electrodes28 a, 30 a, 28 b and 30 b are electrically connected to an electricalcircuit by means of conducting lines 37 a, 35 a, 37 b and 35 b,respectively, the electrical circuit including a switching element so asto alternately switch the electrical connections of conducting lines 37a, 35 a, 37 b and 35 b so as to alternately provide parallel andanti-parallel connections, substantially as described for FIG. 8 a,thereby alternately decreasing and increasing the mechanical impedanceof layers 26 a and 26 b.

FIG. 8 e illustrates another embodiment, wherein the first and secondtransducing cell members are interconnected by means of an anti-parallelconnection. As shown in the figure, the polarity of layer 26 a isopposite to the polarity of layer 26 b so as to reduce the complexity ofthe electrical connections between cell members 25 a and 25 b. Thus,electrode 30 a is connected to electrode 30 b by means of a conductingline 90, and electrodes 28 a and 28 b are provided with conducting lines92 and 94, respectively, for connection to an electrical circuitincluding a switching element, wherein the switching element preferablyfunctions as an on/off switch so as to alternately increase themechanical impedance of layers 26 a and 26 b.

FIG. 8 f shows another embodiment, wherein the first and secondtransducing cell members are interconnected by means of a parallelconnection. As shown, electrodes 30 a and 30 b are interconnected bymeans of conducting line 96, electrodes 28 a and 28 b are interconnectedby means of conducting line 98, and electrodes 30 b and 28 b areprovided with conducting lines 100 and 102, respectively, the conductinglines for connection to an electrical circuit including a switchingelement. The switching element preferably functions as an on/off switchfor alternately decreasing and increasing the mechanical impedance oflayers 26 a and 26 b.

FIG. 9 shows a possible configuration of two transducing cell membersetched onto the same substrate and interconnected by means of ananti-parallel connection. As shown in the figure, the transducing cellmembers are covered by a common piezoelectric layer 26, wherein thepolarity of the portion of layer 26 received between electrodes 30 a and28 a is opposite to the polarity of the portion of layer 26 receivedbetween electrodes 30 b and 28 b. Electrodes 28 a and 28 b are bonded bymeans of a conducting line 80, and electrodes 30 a and 30 b are providedwith conducting lines 44 for connection to an electrical circuit.

Another embodiment of a transmitter element according to the presentinvention is shown in FIG. 10. The transmitter element includes atransducing cell member having a cavity 24 covered by a first and secondpiezoelectric layers, 50 a and 50 b, preferably having oppositepolarities. Preferably, layers 50 a and 50 b are interconnected by meansof an insulating layer 52. Attached to layer 50 a are upper and lowerelectrodes 44 a and 42 a, and attached to layer 50 b are upper and lowerelectrodes 44 b and 42 b. Electrodes 44 a, 42 a, 44 b and 42 b areprovided with conducting lines 54, 55, 56 and 57, respectively, forconnection to an electrical circuit.

It will be appreciated that the above descriptions are intended only toserve as examples, and that many other embodiments are possible withinthe spirit and the scope of the present invention.

As mentioned hereinabove, in those embodiments in which the acoustictransducer 20 is used with device 10, the electrical signal generated bythe acoustic transducer 20 can directly or indirectly activate therelease of the molecules from reservoir 14.

In a direct activation embodiment of device 10 which is specificallyshown in FIG. 11, the electrical signal generated by acoustic transducer20 is communicated directly (via circuitry) to electrodes 21 to therebygenerate the electrical potential.

It will be appreciated that in such cases, the degree of barrierpermeabilization and as such the degree of drug release can becontrolled by the duration and/or frequency of the acoustic signaland/or its intensity received by acoustic transducer 20.

It will further be appreciated that in cases where device 10 includes aplurality of reservoirs, several acoustic transducers can be utilizedsuch that various activation schemes can be employed.

For example, device 10 can include a plurality of acoustic transducers20 each dedicated to a specific reservoir of reservoirs 14. In such acase, each acoustic transducer 20 can function within a specificfrequency range and as such activate release from a specific reservoir14 only upon reception of an acoustic signal of a specific frequency orfrequency range.

Such a configuration enables selective activation of specific reservoirsenabling control over the amount and rate of molecules released as wellas enabling control over the type of molecules released, in cases wherespecific molecules are stored within specific reservoirs.

In an indirect activation embodiment of device 10 shown in FIG. 12, theelectrical signal generated by acoustic transducer 20 serves to activatean energy storage device 104 which in turn generates the electricalpotential between electrodes 21.

In such cases, acoustic transducer 20 preferably forms a part of anacoustic switch 106 which can be configured as described below.

As specifically shown in FIG. 13, acoustic switch 106 includes anelectrical circuit 108 configured for performing one or more functionsor commands when activated.

Acoustic switch 106 further includes an energy storage device 104 (powersource) and an acoustic transducer 20 coupled to electrical circuit 108and energy storage device 104.

In addition, acoustic switch 106 also includes a switch 110, such as theswitch described in the Examples section below, although alternativelyother switches, such as a miniature electromechanical switch and thelike (not shown) may be provided.

Energy storage device 104 may be any of a variety of known devices, suchas an energy exchanger, a battery and/or a capacitor (not shown).Preferably, energy storage device 104 is capable of storing electricalenergy substantially indefinitely. In addition, energy storage device104 may be capable of being charged from an external source, e.g.,inductively, as will be appreciated by those skilled in the art. In apreferred embodiment, energy storage device 104 includes both acapacitor and a primary, non-rechargeable battery. Alternatively, energystorage device 104 may include a secondary, rechargeable battery and/orcapacitor that may be energized before activation or use of acousticswitch 106.

Acoustic switch 106 operates in one of two modes, a “sleep” or “passive”mode when not in use, and an “active” mode, when commanding electricalenergy delivery from energy storage device 104 to electrical circuit 108in order to activate release of molecules from reservoir 14 as describedhereinabove.

When in the sleep mode, there is substantially no energy consumptionfrom energy storage device 104, and consequently, acoustic switch 106may remain in the sleep mode virtually indefinitely, i.e., untilactivated. Thus, acoustic switch 106 may be more energy efficient and,therefore, may require a smaller capacity energy storage device 104 thanpower switching devices that continuously draw at least a small amountof current in their “passive” mode.

To activate the acoustic switch, one or more external acoustic energywaves or signals 112 are transmitted until a signal is received byacoustic transducer 20. Upon excitation by acoustic wave(s) 112,acoustic transducer 20 produces an electrical output that is used toclose, open, or otherwise activate switch 110. Preferably, in order toachieve reliable switching, acoustic transducer 20 is configured togenerate a voltage of at least several tenths of a volt upon excitationthat may be used as an activation signal to close switch 110.

As a safety measure against false positives (either erroneous activationor deactivation), switch 110 may be configured to close only uponreceipt of an initiation signal followed by a confirmation signal. Forexample, an activation signal that includes a first pulse followed by asecond pulse separated by a predetermined delay may be employed.

It will be appreciated that in the case of device 10 of the presentinvention, the use of a confirmation signal may be particularlyadvantageous since it can prevent unintentional release of drugs.

In addition to an activation signal, acoustic transducer 20 may beconfigured for generating a termination signal in response to a secondacoustic excitation (which may be of different frequency or durationthan the activation signal) in order to return acoustic switch 106 toits sleep mode.

For example, once activated, switch 110 may remain closed indefinitely,e.g., until energy storage device 104 is depleted or until a terminationsignal is received by acoustic transducer 20. Alternatively, acousticswitch 106 may include a timer (not shown), such that switch 110 remainsclosed only for a predetermined time, whereupon it may automaticallyopen, returning acoustic switch 106 to its sleep mode.

Acoustic switch 106 may also include a microprocessor unit which servesto interpret the electrical signal provided from acoustic transducer 20(e.g., frequency thereof) into a signal for switching switch 110.

Such interpretation enables to modulate the duration and strength of anelectrical potential provided within reservoir 14 by simply varying thefrequency and/or duration and/or intensity modulation of the acousticsignal provided from outside the body.

Additional acoustic switch configurations which are utilizable by thepresent invention are described in U.S. Pat. No. 6,628,989, thedisclosure of which is expressly incorporated by reference as if fullyset forth herein.

Device 10 of the present invention can form a part of a system forlocalized release of, for example, drugs, which is referred to herein assystem 114.

As shown in FIG. 14, system 114 also includes an extracorporeal unit 116which serves for generating an acoustic signal outside the body, whichacoustic signal is received by device 10 implanted within the body.Numerous devices capable of generating an acoustic signal which canserve as extracorporeal unit 116 are known in the art, and as such nofurther description thereof is given herein.

System 114 can be used as follows. A device 10 filled with molecules isimplanted within a specific body tissue. Following implantation,extracorporeal unit 116 generates an acoustic signal of a predeterminedfrequency and/or duration thereby activating release of the moleculesfrom device 10 as described hereinabove.

Thus, the present invention provides a device, system and method usefulfor localized delivery of molecules such as drugs.

The device of the present invention provides several advantages overprior art devices such as those described in U.S. Pat. Nos. 6,123,861and 5,797,898. Such advantages are afforded by the acoustic transducercomponent of the device which functions in converting an acoustic signalinto an electrical activation signal.

In sharp contrast, the device described in U.S. Pat. Nos. 6,123,861 and5,797,898, employs radiofrequency (RF) receivers which activate drugrelease upon reception of an RF signal generated outside the body. Theuse of RF activation is disadvantageous since RF signals are, at leastin part, absorbed by body tissues and are directionally limited by bulkyunidirectional antennas used for reception.

On the other hand, acoustic transducers, such as the one utilized by thedevice of the present invention, are omni-directional receivers which donot require antennas and as such do not suffer from structural andfunctional limitations which are inherent to RF receivers.

In addition, acoustic activation requires far less energy than RFactivation since acoustic waves, unlike RF waves, propagate well withinthe aqueous medium which forms a substantial part of body tissues.

Additional objects, advantages, and novel features of the presentinvention will become apparent to one ordinarily skilled in the art uponexamination of the following examples, which are not intended to belimiting. Additionally, each of the various embodiments and aspects ofthe present invention as delineated hereinabove find experimentalsupport in the following examples.

EXAMPLES Acoustic Switch Circuitry and Function

Referring again to the drawings, FIG. 15, illustrates an example ofcircuitry and components employed by an acoustic switch 200 which isutilizable by the device of the present invention.

Switch 200 includes a piezoelectric transducer, or other acoustictransducer such the acoustic transducer described hereinabove (notshown, but connectable at locations piezo + and piezo −), a plurality ofMOSFET transistors (Q1-Q4) and resistors (R1-R4), and switch S1.

In the switch's “sleep” mode, all of the MOSFET transistors (Q1-Q4) arein an off state. To maintain the off state, the gates of the transistorsare biased by pull-up and pull-down resistors. The gates of N-channeltransistors (Q1, Q3 & Q4) are biased to ground and the gate of P-channeltransistor Q2 is biased to +3V. During this quiescent stage, switch S1is closed and no current flows through the circuit.

Therefore, although an energy storage device (not shown, but coupledbetween the hot post, labeled with an exemplary voltage of +3V, andground) is connected to the switch 200, no current is beingdrawn-therefrom since all of the transistors are quiescent.

When the piezoelectric transducer detects an external acoustic signal,e.g., having a particular frequency such as the transducer's resonantfrequency, the voltage on the transistor Q1 will exceed the transistorthreshold voltage of about one half of a volt. Transistor Q1 is therebyswitched on and current flows through transistor Q1 and pull-up resistorR2. As a result of the current flow through transistor Q1, the voltageon the drain of transistor Q1 and the gate of transistor Q2 drops from+3V substantially to zero (ground). This drop in voltage switches on theP-channel transistor Q2, which begins to conduct through transistor Q2and pull-down resistor R3.

As a result of the current flowing through transistor Q2, the voltage onthe drain of transistor Q2 and the gates of transistors Q3 and Q4increases from substantially zero to +3V. The increase in voltageswitches on transistors Q3 and Q4. As a result, transistor Q3 begins toconduct through resistor R4 and main switching transistor Q4 begins toconduct through the “load,” thereby switching on the electrical circuit.

As a result of the current flowing through transistor Q3, the gate oftransistor Q2 is connected to ground through transistor Q3, irrespectiveof whether or not transistor Q1 is conducting. At this stage, thetransistors (Q2, Q3 & Q4) are latched to the conducting state, even ifthe piezoelectric voltage on transistor Q1 is subsequently reduced tozero and transistor Q1 ceases to conduct. Thus, main switchingtransistor Q4 will remain on until switch S1 is opened.

In order to deactivate or open switch 200, switch S1 must be opened, forexample, while there is no acoustic excitation of the piezoelectrictransducer. If this occurs, the gate of transistor Q2 increases to +3Vdue to pull-up resistor R2. Transistor Q2 then switches off, thereby, inturn, switching off transistors Q3 and Q4. At this stage, switch 200returns to its sleep mode, even if switch SI is again closed. Switch 200will only return to its active mode upon receiving a new acousticactivation signal from the piezoelectric transducer.

It should be apparent to one of ordinary skill in the art that theabove-mentioned electrical circuit is not the only possibleimplementation of a switch for use with the present invention. Forexample, the switching operation may be performed using a CMOS circuit,which may draw less current when switched on, an electromechanicalswitch, and the like.

It is appreciated that certain features of the invention, which are, forclarity, described in the context of separate embodiments, may also beprovided in combination in a single embodiment. Conversely, variousfeatures of the invention which are, for brevity, described in thecontext of a single embodiment, may also be provided separately or inany suitable subcombination.

Although the invention has been described in conjunction with specificembodiments thereof, it is evident that many alternatives, modificationsand variations will be apparent to those skilled in the art.Accordingly, it is intended to embrace all such alternatives,modifications and variations that fall within the spirit and broad scopeof the appended claims. All publications, patents and patentapplications mentioned in this specification are herein incorporated intheir entirety by reference into the specification, to the same extentas if each individual publication, patent, or patent application wasspecifically and individually indicated to be incorporated herein byreference. In addition, citation or identification of any reference inthis application shall not be construed as an admission that suchreference is available as prior art to the present invention.

1. An implantable medical device, comprising: an acoustic transducerconfigured to receive an acoustic interrogation signal; and a means formodulating a reflected acoustic wave from the acoustic transducer, thereflected acoustic wave including data to be transmitted from theimplantable medical device.
 2. The implantable medical device of claim1, wherein the means for modulating a reflected acoustic wave comprisesa switching element coupled to the acoustic transducer.
 3. Theimplantable medical device of claim 2, wherein the acoustic transducerincludes a piezoelectric layer, and wherein the switching element isconfigured to controllably change the mechanical impedance of thepiezoelectric layer based on the data.
 4. The implantable medicaldevice, of claim 2, further comprising a sensor configured for sensingat least one parameter and generating an electrical sensor signal, andwherein the switching element is configured to controllably change themechanical impedance of the piezoelectric layer based on the frequencyof the electrical sensor signal.
 5. The implantable medical device ofclaim 1, wherein the acoustic transducer is configured to convert theacoustic interrogation signal into an electrical signal for providingelectrical power to one or more components of the implantable medicaldevice.
 6. The implantable medical device of claim 1, wherein theacoustic transducer comprises: a cell member including at least onecavity; a flexible piezoelectric layer coupled to the cell member, thepiezoelectric layer having an external surface and an internal surface;and a first electrode attached to the external surface of thepiezoelectric layer and a second electrode attached to the internalsurface of the piezoelectric layer.
 7. The implantable medical device ofclaim 6, wherein the piezoelectric layer has a resonance at or near awavelength of the acoustic interrogation signal.
 8. The implantablemedical device of claim 7, wherein the piezoelectric layer has aflexibility such that the resonant wavelength is larger than a dimensionof the acoustic transducer.
 9. The implantable medical device of claim6, wherein the piezoelectric layer has a concave shape.
 10. Theimplantable medical device of claim 6, wherein the cavity includes agas.
 11. The implantable medical device of claim 6, wherein at least oneof the first and second electrodes covers only a portion of a surface ofthe piezoelectric layer.
 12. An implantable medical device, comprising:at least one sensor configured for sensing at least one parameter of aphysiological condition and for generating an electrical sensor signalrepresentative of the physiological condition; an acoustic transducercoupled to the at least one sensor, the acoustic transducer configuredto convert a received acoustic interrogation signal into an electricalsignal; a means for modulating a reflected acoustic wave from theacoustic transducer based on the electrical sensor signal, the reflectedacoustic wave including one or more encoded sensor measurements sensedby the at least one sensor.
 13. The implantable medical device of claim12, wherein the means for modulating a reflected acoustic wave comprisesa switching element coupled to the acoustic transducer.
 14. Theimplantable medical device of claim 13, wherein the acoustic transducerincludes a piezoelectric layer, and wherein the switching element isconfigured to controllably change the mechanical impedance of thepiezoelectric layer based on the frequency of the electrical sensorsignal.
 15. The implantable medical device of claim 12, wherein theacoustic transducer is configured to convert the acoustic interrogationsignal into an electrical signal for providing electrical power to oneor more components of the implantable medical device.